Effects of high-amount-high-intensity exercise on in vivo platelet activation: modulation by lipid peroxidation and AGE/RAGE axis

: Physical activity is associated with cardiovascular risk reduction, but the effects of exercise on platelet activation remain controversial. We investigated the effects of regular high-amount, high intensity aerobic exercise on in vivo thromboxane (TX)-dependent platelet activation and plasma levels of platelet-derived proteins, CD40L and P-selectin, and whether platelet variables changes may be related to changes in high-density lipoprotein (HDL) and in the extent of oxidative stress and oxidative stress-related inflammation, as reflected by urinary isoprostane excretion and endogenous soluble receptor for advanced glycation end-products (esRAGE), respectively. Urinary excretion of 11-dehydro-TXB₂ and 8-iso-prostaglandin (PG)F(2α) and plasma levels of P-selectin, CD40L and esRAGE were measured before and after a eight-week standardised aerobic high-amount-high-intensity training program in 22 sedentary subjects with low-to-intermediate risk. Exercise training had a clear beneficial effect on HDL cholesterol (+10%, p=0.027) and triglyceride (-27%, p=0.008) concentration. In addition, a significant (p<0.0001) decrease in urinary 11-dehydro-TXB₂ (26%), 8-iso-PGF(2α) (21%), plasma P-selectin (27%), CD40L (35%) and a 61% increase in esRAGE were observed. Multiple regression analysis revealed that urinary 8-iso-PGF(2α) [beta=0.33, SEM=0.116, p=0.027] and esRAGE (beta=-0.30, SEM=31.3, p=0.046) were the only significant predictors of urinary 11-dehydro-TXB₂ excretion rate over the training period. In conclusion, regular high-amount-high-intensity exercise training has broad beneficial effects on platelet activation markers, paralleled and possibly associated with changes in the lipoprotein profile and in markers of lipid peroxidation and AGE/RAGE axis. Our findings may help explaining why a similar amount of exercise exerts significant benefits in preventing cardiovascular events.